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Laboratory of Molecular Biophysics
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This is the 29th edition of the Laboratory of Molecular Biophysics Annual Report. It describes the activities in the Laboratory during the period August 1999 to August 2000. Contributions are listed in alphabetical order by the group leaders name.
This year we have welcomed several a new members and research fellows whose work broadens the activities of the Laboratory.
Jim McDonnell from the Rockefeller University, New York, has been appointed University Lecturer in Molecular Biophysics (vice Barford). His work focuses on molecular recognition in the immune system and programmed cell death. Current studies involve the structural and functional characterisation of proteins regulating inflammation and allergic responses, especially those mediated by the IgE network of proteins and their receptors, using NMR spectroscopic approaches. In a second programme Jim's work builds on his structure of the pro-apoptotic member of the BCL-2 family, BID, to design small molecule mimics in order to develop new anti-apoptotic compounds and agents for dissecting roles of BID in signalling pathways.
Rick Lewis has been awarded a Wellcome Trust Career Development Award and
rejoins us from York, where he carried out post-doctoral studies having
completed his DPhil in Oxford with Dale Wigley. His work addresses the
structural basis of phospho-signalling in prokaryotes using the stress induced
mechanisms of 
B-dependent family of proteins in
Bacillus subtilis as an important biological example.
Jasper van Thor has joined us from Amsterdam as an EMBO Fellow and subsequently as a Human Frontiers Science Programme Fellow. Building on his experience with spectroscopic studies on light sensitive proteins, he is now applying X-ray crystallography to unravel the structural basis of the light signalling mechanisms in both simple systems such as the green fluorescent protein and more complex systems such as the phytochrome-like protein Ppr that signals through a protein kinase domain, work that fits with the studies of Louise Johnson, Jane Endicott and Martin Noble on eukaryotic protein kinases.
Thomas Lykke-Moller Sorensen has joined us from Aarhus, Denmark as an EMBO Fellow to work with Declan Doyle on P-type ATPases, work which relates to his previous studies on the characterisation through mutagenesis of the mechanisms for intramolecular communication in the sarcoplasmic reticulum Ca2+ ATPase.
We also welcome back Phil Biggin who has rejoined Mark Sansom's group as a Wellcome Trust International Fellow. Phil has been working for the last two years in Dr S. Choe's lab at the Salk Institute, San Diego on modelling and simulation studies on potassium channels.
Hyun Ji Kim has joined Mark Sansom's group funded by an MRC Training Fellowship for Bioinformatics. Previously she worked with Dr J. Gross in Biochemistry, Oxford on signalling in Dictostelium.
Mike Pickford, our senior workshop technician, retired this year after 34 years with LMB and 43 years with the University. Mike was the mainstay of instrument development in the Laboratory. In the early years he participated with David Phillips in the modification of the linear diffractometer to measure 5 reflections simultaneously (a considerable advance in those days), then with early work on low temperature devices to the more recent studies that led to the instruments used routinely in the Laboratory and elsewhere for cryo-crystallography. One of the recent highlights of his work was the design and construction of an oxygen pressure device that enable oxygen to be bound to crystals of isopenicillin synthase at pressures up to 60 bar, work for which Mike was co-author of a Nature paper (Burzlaff et al. (1999) Nature 401, 721). Mike will be remembered with affection by all who knew him. We are pleased to announce that Mike Pritchard has been appointed as his successor.
We were also sad to say goodbye to Yuguang Huang, who had been the Oxford Centre for Molecular Sciences assistant to Richard Bryan for running the OCMS computer and graphics facility. Yuguang was much appreciated for his friendliness to users and his skill in sorting problems. He cared for the Unix systems with exemplary efficiency. He has joined the NTL Company in London where he can be near his family. Guy Coates has been appointed as the new assistant. Guy joins us from the University of Birmingham where he worked on computational studies on structure function relationships in ion channels.
We have continued our programme of creating more wet biochemistry space for protein expression and purification. The Laboratory on the third floor, T1, has been refurbished to create space for the groups of Susan Lea, Kim Watson and Rick Lewis. We have also made a new initiative in providing for electron microscopy in LMB. The workshop space in the basement has been divided and one half of the space refurbished to house the Phillips CM120 cryoelectron microscope from the Institute of Virology with the kind permission of Professor Pat Nuttall. Catherine Vénien-Bryan describes our developing interests in electron microscopy in her section. Progress in imaging a number of molecules and macromolecular complexes has been achieved.
The Laboratory has become involved in the graduate training programme following the award from the Wellcome Trust of a graduate training scheme in Structural Biology. Mark Sansom is the current organiser of the programme that provides students with courses and rotation projects in their first year before embarking on a 3 year D. Phil. programme. Members of the Laboratory have also been active in organising outside courses. Martin Noble and Jane Endicott were co-organisers of the British Crystallographic Association Winter meeting on Structural Biology in December 1999. Louise Johnson was Director (with co-directors D. I. Stuart, D. Turk and M. Jaskolski) of the School of Macromolecular Crystallography at Erice, Sicily in May 2000, and Elspeth Garman is frequently in demand for summer schools and training courses such as the BCA Summer School in Crystallography.
The work of the Laboratory addresses structural aspects of a number of diverse
biological problems. These include the proteins of the cell cycle, proteins
of signal transduction pathways, macromolecular complexes involved in
selective ubiquitination, membrane ion channels, enzyme mechanism, (e.g.
protein kinases; arylamine N-acetyl transferase, glucose-6-phosphate
dehydrogenase), proteins of the inflammatory response, signalling proteins of
the pancreatic 
cell, host pathogen interactions, proteins of the complement
system, proteins of the bacterial chemosensing pathway, protein assemblies at
the zeta chain of the T cell receptor, interactions of focal adhesion kinase,
and structure based drug design. Our major techniques are protein
crystallography and molecular dynamics simulations. These are complemented by
expression; purification and characterisation studies to produce sufficient
quantities of target proteins for crystallisation, kinetic and binding
studies. The structures form the starting point for understanding the
molecular basis of the control, catalytic and recognition phenomena that govern
the life of the cell. Underlying the research is the provision of
infrastructure facilities that include the large scale computing required for
molecular dynamics simulations of membrane proteins, the crystallographic
computing facilities with emphasis on visual representation, and the X-ray
crystallographic facilities. The individual entries provide the details of
research accomplished last year.
The Laboratory Report is not a formal publication and permission to reproduce material should be sought from the authors.
Finally I thank Richard Bryan, Jane Thorp and all members of the Laboratory for their help in preparing the Report. It is always immensely rewarding to see the work of the Laboratory brought together.
Louise N. Johnson
November 2000